Hereditary retinal degenerations are major causes of blindness for which there is no effective treatment. Intravitreous injection of neuro- trophic factors has been shown to slow retinal degeneration in some animal models. I plan to use transgenic mice with an inducible promoter combined with one that directs production of high levels of neurotrophic factors specifically in the retina to temporally modulate the level of neurotrophic factor expression and address the following questions. (1) What is the effect of sustained increased production of neurotrophic factors in the retina of mice with inherited retinal degenerations? (2) Are there differences in the effectiveness of several known neurotrophic factors? (3) Are combinations of neurotrophic factors better than single factors alone? (4) What is the effect of sustained increased production of neurotrophic factors started at various times after the onset of retinal degeneration? This will help to determine what effects are likely to be when treatment is started relatively late in the course of retinal degenerations. (5) What is the effect of intermittent increased production of neurotrophic factors in retinal degenerations? This will help to determine if intermittent injections might be possible or whether implantation of a sustained delivery device or gene therapy is likely to be needed. These experiments will help to determine if neurotrophic factors provide a viable approach for treatment of patients with retinal degenerations and help to answer several questions that are critical in the design of clinical trials.